Liver-predominant Disease Research Articles

Chemosaturation with percutaneous hepatic perfusion of melphalan for metastatic uveal melanoma.

Uveal melanoma, the most common primary ocular malignancy in adults, carries a poor prognosis: 50% of patients develop the metastatic disease with a 10-25% 1-year survival and no established standard of care treatment. Prior studies of melphalan percutaneous hepatic perfusion (M-PHP) have shown promise in metastatic uveal melanoma (mUM) patients with liver predominant disease but are limited by small sample sizes. We contribute our findings on the safety and efficacy of the procedure in the largest sample population to date. A retrospective analysis of outcome and safety data for all mUM patients receiving M-PHP was performed. Tumour response and treatment toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events v5.03, respectively. 250 M-PHP procedures were performed in 81 patients (median of three per patient). The analysis demonstrated a hepatic disease control rate of 88.9% (72/81), a hepatic response rate of 66.7% (54/81), and an overall response rate of 60.5% (49/81). After a median follow-up of 12.9 months, median overall progression-free (PFS) and median overall survival (OS) were 8.4 and 14.9 months, respectively. There were no fatal treatment-related adverse events (TRAE). Forty-three grade 3 (29) or 4 (14) TRAE occurred in 23 (27.7%) patients with a significant reduction in such events between procedures performed in 2016-2020 vs. 2012-2016 (0.17 vs. 0.90 per patient, P < 0.001). M-PHP provides excellent response rates and PFS compared with other available treatments, with decreasing side effect profile with experience. Combination therapy with systemic agents may be viable to further advance OS.

The Landmark Series: Neuroendocrine Tumor Liver Metastases.

Neuroendocrine tumors are becoming increasingly prevalent, with many patients presenting with or developing metastatic disease to the liver. In this landmark series paper, we highlight the critical studies that have defined the surgical management of neuroendocrine tumor liver metastases, as well as several randomized control trials which have investigated strategies for systemic control of metastatic disease. Liver-directed surgical approaches and locally ablative procedures are recommended for patients with limited, resectable, and in some cases, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, chemoembolization, and radioembolization, offer another approach for management in patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising therapy for patients with hepatic and/or extrahepatic metastases. Various systemic medical therapies are also available as adjunct or definitive therapy for patients with metastatic disease. This article reviews current data regarding management of neuroendocrine liver metastases and highlights areas for future study.

A Pilot Feasibility Study of Yttrium-90 Liver Radioembolization Followed by Durvalumab and Tremelimumab in Patients with Microsatellite Stable Colorectal Cancer Liver Metastases.

Radioembolization with yttrium-90 resin microspheres can be combined safely with full doses of durvalumab and tremelimumab in patients with metastatic colorectal cancer. Regional radioembolization with yttrium-90 resin microspheres did not result in any hepatic or extrahepatic responses to a combination of durvalumab and tremelimumab. The lack of immunomodulatory responses to yttrium-90 on biopsies before and after treatment rules out a potential role for this strategy in converting a "cold tumor" into an "inflamed," immune responsive tumor. PD-1 inhibitors have been ineffective in microsatellite stable (MSS) metastatic colorectal cancer (CRC). Preclinical models suggest that radiation therapy may sensitize MSS CRC to PD-1 blockade. Patients with MSS metastatic CRC with liver-predominant disease who progressed following at least one prior line of treatment were treated with yttrium-90 (Y90) radioembolization to the liver (SIR-Spheres; Sirtex, Woburn, MA) followed 2-3 weeks later by the combination of durvalumab and tremelimumab. A Simon two-stage design was implemented, with a planned expansion to 18 patients if at least one response was noted in the first nine patients. Nine patients enrolled in the first stage of the study, all with progressive disease (PD) during or after their first two cycles of treatment. Per preplanned design, the study was closed because of futility. No treatment-related grade 3 or greater toxicities were recorded. Correlative studies with tumor biopsies showed low levels of tumor-infiltrating lymphocyte (TIL) infiltration in tumor cancer islands before and after Y90 radioembolization. Y90 radioembolization can be added safely to durvalumab and tremelimumab but did not promote tumor-directed immune responses against liver-metastasized MSS CRC.

Abstract 528: Radioembolization followed by durvalumab and tremelimumab does not induce immune responses against liver-metastasized MSS colorectal cancer

Abstract Introduction: PD-1 inhibitors have been ineffective in microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Preclinical models suggest that radiation therapy may sensitize MSS CRC to PD-1 blockade. This constitutes the rationale for combining radioembolization to the liver in patients (pts) with MSS CRC with liver metastasis. Methods: Pts with MSS mCRC with liver predominant disease who progressed following at least 1 prior line of treatment, were eligible for study treatment. Treatment consisted of Y90 radioembolization to the liver (SIRTEX®) followed 2-3 weeks later by the intravenous (IV) combination of durvalumab (D) at 1500 mg and tremelimumab (T) at 75 mg Q4W for 4 months, followed by D 1500 mg Q4W x 8 cycles, or until disease progression (PD). Tumor biopsies were obtained at baseline, 1-2 weeks post SIR-Spheres®, and 2-3 weeks after D+T. A Simon 2-stage design was implemented, with a planned expansion to 18 patients if at least 1 response is noted in the 1st 9 pts. Correlative studies included tumor and peripheral blood flow cytometry, serum cytokine assays, and tumor IHC multiplex assay for CD8, CD4, CD68 and Cytokeratin20 expression. Immune and cancer related gene expression of the tumor microenvironment was analyzed via NanoString. Results: 9 pts enrolled in the 1st stage of the study, all with PD within or after their first 2 cycles of treatment. Per pre-planned design, the study was closed for futility. Here we report our correlative study for this trial. Based on IHC, intratumoral TILs (CD4 and CD8 T cells) were not detectable on any of the serial tumor biopsies (pre-Y90, post-Y90, and post D+T), while heavy CD68+ macrophage infiltration was consistently observed. Such observations were statistically validated by comparing paired serial samples using NanoString. Increased expression of collagen genes, such as COL1A1, COL1A2, and COL3A1, following Y90 was noted, as reported in literatures for cases with chemo and radiation resistance. MDM2, known to associate with resistance to PD-1/PD-L1 inhibitors, was also upregulated following Y90. Furthermore, flow cytometry results showed no difference in CD4+ T cells, CD8+T cells, CD20+B cells, CD33+HLA-DR-MDSCs, and CD4+Foxp3+ regulatory T cells based on paired serial PBMC samples. However, we observed a significant increase in PD-1+CD4+ and PD-1+CD8+ T cell subpopulations in PBMC following D+T, which agrees with other reports that PD-1/PD-L1 targeting leads to the expansion of PD-1+ T cells. In addition, CD3-CD56+ NK cell population was increased following D+T when compared with Y90. Conclusion: Y90 radioembolization can be added safely to D+T but did not promote tumor-directed immune responses against liver-metastasized MSS CRC. The associated correlative studies do not support a role for Y90 radioembolization to convert immunologically ‘cold’ tumors into ‘hot’ tumors. Citation Format: Chongkai Wang, John Park, Ching Ouyang, Raju Pillai, Jeffrey Longmate, Holly Yin, Christian Avalos, Maricel Gozo, Colt Egelston, Peter P. Lee, Marwan G. Fakih. Radioembolization followed by durvalumab and tremelimumab does not induce immune responses against liver-metastasized MSS colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 528.

Thermal Ablations for Colorectal Liver Metastases

AbstractApproximately 25% of colorectal cancers patients will develop hepatic metastases in the course of their disease. Surgical resection of hepatic metastases remains the first treatment choice for these patients, when feasible. However, only approximately 30% of metastatic lesions are resectable at the time of diagnosis. Thermal ablations have played an increasing role over the last few decades in the palliative and curative setting of colorectal liver metastases (CRLMs) in nonsurgical candidates with a liver-predominant disease. Several different techniques have been used to perform image-guided thermal ablations in the liver, including radiofrequency ablation, microwave ablation, cryoablation, and laser thermal ablation. We review the current ablation techniques, image-guidance modalities, indications, and debated topics of image-guided thermal ablation in CRLMs. Moreover, recent results from clinical trials are discussed along with future trends in liver thermal ablations.

Complete response in a patient with liver metastases from breast cancer employing hepatic arterial infusion 5-fluorouracil based chemotherapy plus systemic nab-paclitaxel.

About half of patients with metastatic breast cancer (mBC) have unresectable liver metastases (LMs) or liver-predominant disease (LPD). Unfortunately systemic chemotherapy has limited tumor response due to LMs are supplied by hepatic artery. Hepatic intra-arterial (HAI) have antitumor activity in pretreated patients with LMs. Here we report the case of a 55-year-old woman affected by BCLPD and heavily pretreated. LMs responded to treatment based on HAI with 5-fluorouracil and nab-paclitaxel systemic chemotherapy, and they completely disappeared on a CT-scan. We conclude that this combination chemotherapy is safe and may be very useful for the treatment of patients with BCLPD. Therefore, this combination should be evaluated in a large study.

Treatment Strategies for Metastatic Neuroendocrine Tumors of the Gastrointestinal Tract.

The therapeutic landscape of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) has evolved significantly in recent years. Current and emerging treatment options include somatostatin analogs, radiolabeled somatostatin analogs, the mTOR inhibitor everolimus, and the tyrosine kinase inhibitor sunitinib. Although high-quality data from phase III trials are lacking, cytotoxic agents are commonly used for the treatment of poorly differentiated neuroendocrine carcinomas and well-differentiated NETs originating in the pancreas. Hepatic-directed therapies are recommended for patients with slow-growing, liver-predominant disease but have never been compared to systemic agents. Telotristat ethyl, a novel serotonin synthesis inhibitor, has recently demonstrated efficacy in palliating diarrhea in patients with poorly controlled carcinoid syndrome. In the absence of definite predictive biomarkers, therapeutic decisions in most cases rely on clinical and pathological criteria. However, navigating the current therapeutic algorithm may be challenging, and future trials need to address several important questions: what is the best sequence of treatment? Is there a role for combination therapies in GEP-NETs? Are neoadjuvant, adjuvant, or maintenance strategies safe and effective? Do all NET patients require active treatment? What new molecular targets can be clinically exploited? A tight integration between basic and clinical research is needed to further advance the field of NETs.

Sequencing cell free DNA in patients receiving selective internal radiation therapy for colorectal liver metastases.

646 Background: Tumour heterogeneity is a key determinants of cancer resistance. Serial sampling of cell free (cf)DNA may detect evolving somatic mutations. Monitoring cancers after therapies e.g. selective internal radiation therapy (SIRT) require new biomarkers as RECIST imaging was developed to assess response to chemotherapy and may not reflect tumour changes due to new therapeutic strategies. The utility of cfDNA to detect recurrence and predict response is emerging. The objective of this study was to sequence serial cfDNA samples from patients with liver predominant metastatic disease receiving SIRT, and explore the feasibility of using this method to detect evolution of somatic mutations after high dose radiation. Methods: A prospective imaging biomarker study was performed in patients with colorectal liver metastases (CRLM) receiving SIRT. Plasma was extracted and frozen within 4 hours at 3 time points: baseline, 4 and 10 weeks after SIRT. Ion Torrent Amplicon sequencing was performed using cancer hotspot panel v.2. Sequencing of primary tumours was obtained by pyrosequencing. Results: Twenty-four patients with CRLM were recruited from March – Dec 2015, and 18 had cfDNA extracted for sequencing at a minimum of two time points. Ion Torrent amplicon sequencing of baseline cfDNA showed high concordance with formalin-fixed paraffin-embedded (FFPE) tumour samples. Serial cfDNA sequencing in a patient with partial response by imaging, detected 22% KRAS G12C mutation at baseline, which decreased to 1.5% by 4 weeks, then was undetectable 10 weeks after SIRT. Sequencing of another patient’s cfDNA revealed persistence of KRAS G13D and a truncating APCmutation at both 4 and 10 weeks after SIRT, consistent with the patient’s progressive disease. Conclusions: Cell-free DNA is emerging as a biomarker in colorectal cancer. Our measurements of mutational status in baseline cfDNA and FFPE samples show high concordance. This study reports that serial cfDNA sequencing detects changes in mutational status and specific mutations following high dose radiation to the liver. This adds to the evidence of cfDNA as a tool to detect evolution of somatic mutations following therapy.

Management of neuroendocrine tumors.

Current strategies for managing neuroendocrine tumors (NETs) in adult patients are reviewed, with a focus on medication safety concerns. NETs usually originate in the gastrointestinal or bronchopulmonary tract. Symptoms due to hormonal hypersecretion often occur in patients with foregut or midgut NETs or liver metastases. Surgical resection is recommended for most localized NETs, while systemic cytotoxic chemotherapy is typically used for high-grade and pancreatic tumors. The standard of care for metastatic NETs is somatostatin analog therapy with octreotide (available in both short- and long-acting formulations) or a depot formulation of lanreotide. Everolimus and sunitinib are targeted therapies with approved indications for use in treating advanced pancreatic NETs. Some patients with liver-predominant disease or liver metastases may undergo regional chemoembolization procedures. Pharmacists should be cognizant of differences between newer and older chemoembolization agents and procedures, as well as differences between somatostatin analog products used as medications and the radiolabelled forms used in diagnostic scintigraphy. Other medication safety issues in NET management arise during perioperative supportive care, patient education, compliance counseling, and management of adverse effects of targeted therapies and chemotherapy, including stomatitis, hyperthyroidism, and hand-foot skin reaction. Somatostatin analog therapy is the mainstay for management of locally advanced or metastatic NETs. Liver-directed therapy is an option for localized unresectable disease; platinum-based chemotherapy is the first-line treatment for poorly differentiated tumors. Optimal sequencing of these treatments and targeted therapies such as everolimus and tyrosine kinase inhibitors remains to be elucidated.

Somatostatin receptor PET/MRI for the evaluation of neuroendocrine tumors

With the introduction of simultaneous PET/MRI scanners, concurrent acquisition of PET and MRI data is feasible, allowing for improved patient convenience and decreased radiation dose. Although PET/MRI has been used in many settings, not all cancers benefit from the combined modality. With the availability of somatostatin receptor-targeted PET tracers such as 68Ga-DOTA-TOC and 68Ga-DOTA-TATE, imaging of NET patients has refocused on targeted imaging, particularly with the development of peptide receptor radiotherapy. Nonetheless, there are many patients who continue to benefit from dedicated MR imaging, such as those with liver-predominant disease. In these patients, SSR PET/MRI is an important option for optimal imaging. Both diffusion-weighted imaging and hepatobiliary phase imaging provide improved lesion detection compared to conventional MRI and CT, and the results can effect therapeutic decisions. Additionally, the use of motion correction techniques can be used to leverage the additional PET data acquired in dedicated liver PET/MRI to remove respiratory artifacts.

Phase Ib trial of gemcitabine with yttrium-90 in patients with hepatic tumors of pancreatobiliary origin.

460 Background: The rationale for combining Gemcitabine (G) with Yttrium-90 (Y90) is based on G being a potent radio sensitizer and activity of Y90 against liver tumors of pancreatobiliary histology. Therefore, a safety and efficacy trial of adding G to Y90 is required. Methods: Eligibility: Chemo-naïve patients with histologic diagnosis of unresectable PC or CC with liver predominant disease. Design: Open label phase I design with 3+3 G dose escalation. Induction G on Day 1 followed by Y90 on Day 2 and subsequent pre-assigned dose levels of G until week 12. Primary objective: To determine the maximal tolerated dose of G that can be used in combination with Y90. Secondary objectives: To characterize the toxicity, evaluate hepatic progression free survival (HPFS); determine tumor response rate using RECIST and PERCIST criteria; determine the progression free survival (PFS) and overall survival (OS). Correlative Imaging: 18-FDG PET/CT with contrast at baseline and 12 weeks. Results: 14 patients were recruited and 8 met the inclusion criteria. Seven out of eight patients tolerated the dose escalation regime of G (dose level 1-400 and dose level 2-600mg/m2). All the patients developed grade 1 toxicities (Hepatobiliary 25%, Bone marrow 25%, Fatigue 100%). Three patients (37.5 %) had grade 2 hepatobiliary toxicity and one patient (12.5 %) had grade 3 hepatobiliary toxicity, which required short-term hospitalization. No radiation pneumonitis, gastrointestinal ulceration, or procedure-related mortality occurred. Six patients (75%) developed grade 1 toxicity (fatigue). All of the patients had SD in the liver by RECIST; the objective response rate was 62.5% by PERCIST (CR12.5%, PR50%, SD25% PD12.5%). Overall objective response rate was 0% by RECIST (SD62.5%, PD37.5%); and 50% for PERCIST (CR12.5%, PR37.5%, SD12.5%, PD37.5%). The median OS from diagnosis was 13.8 months (95% CI, 9.65 to 26.29 months) and from Y90 therapy 10.9 months (95% CI, 6.47 to 22.39 months). PFS was 6.92 months (95%CI, 4.37-16.5 months) and HPFS of 8.72 months (95%CI, 4.48-19.36 months). Conclusions: In patients with hepatic tumors of pancreatobiliary origin, Gemcitabine at 600mg/m2 with Y90 therapy appears to be a viable and safe therapy. Clinical trial information: NCT01434459.

Selective Internal Radiation Therapy for the Treatment of Inoperable Neuroendocrine Tumor Liver Metastases

Neuroendocrine tumor liver metastases are commonly present at the time of neuroendocrine tumor diagnosis. Surgical resection is potentially curative and achieves the best long-term results but is not feasible in many patients. Angiographic liver-directed treatment modalities such as transarterial embolization, transarterial chemoembolization and selective internal radiotherapy using Yttrium-90 ([90]Y)-labeled microspheres have been shown to be effective treatments with liver predominant disease. Here, we review the management of neuroendocrine tumor liver metastases including selective internal radiotherapy.

Hepatic arterial infusion therapy in advanced cancer and liver-predominant disease: the MD Anderson Experience.

Liver metastases in patients with cancer are associated with a poor prognosis. We assessed the clinical outcomes in patients with advanced cancer and predominant liver involvement treated on hepatic arterial infusion (HAI chemotherapy protocols. We retrospectively analyzed the outcomes of patients referred to the Phase I Clinical Trials Program between April 2004 and September 2009. Overall, 202 consecutive patients were identified. Of 189 evaluable patients, the rates of partial response (PR) and stable disease (SD) >4 months were 6.3% and 23%, respectively. In patients with hepatocellular carcinoma or cholangiocarcinoma (n = 15), 5 (33%) had SD ≥ 4 months. In patients with colorectal cancer (n = 67) treated with HAl oxaliplatin or irinotecan combination therapy, the rates of PR and SD ≥ 4 months were 7.5% and 34.3%, respectively. In patients with breast cancer (n = 17) treated with HAI cisplatin-based therapy, the rates of PR and SD -4 months were 17.6% and 35.3%, respectively. The median survival of patients with PR and SD ≥ 4 months was 11.6 months. Independent factors predicting shorter survival were male gender; decreased albumin and hemogloblin; and elevated bilirubin, lactate dehydrogenase and alanine aminotransferase. HAI combination therapies have antitumor activity in selected heavily pretreated patients with certain tumor types and liver involvement.

Multimodality imaging and radiological-pathological analysis of ethiodized oil: Imaging biomarker of tumor necrosis after TACE?

TPS503 Background: In transarterial chemoembolization (TACE) for primary and metastatic liver malignancies ethiodized oil (Lipiodol) serves 3 roles: vehicle to deliver high concentration of the chemotherapeutic agent to the tumor, embolic agent to the tumor feeding artery and a contrast agent. The latter allows for intraprocedural visualization during drug delivery. Because of increased retention in liver tumors, Lipiodol can be visualized post-TACE for several weeks to months. Controversial preclinical and clinical data have been published about the role of Lipiodol as an imaging biomarker for treatment success after TACE. Here we investigate whether increased tumor Lipiodol deposition correlates with tumor response and survival using multimodality imaging and radiological/pathological correlation. Methods: This is a prospective phase 2, single center, IRB-approved study. Inclusion criteria include adult patients (Child-Pugh class of A or B and ECOG performance status of 0-2) with unresectable HCC with liver predominant disease or hepatic metastases from any solid tumor. Dynamic contrast-enhanced (DCE) MRI and CT of the liver and PET-CT were obtained before TACE. 24 hours after TACE, a noncontrast CT of the liver was obtained to quantify Lipiodol retention in the targeted tumor. Follow-up imaging consisting of DCE-MRI, CT and PET–CT were also performed approximately 1, 3 and 6 months after the last TACE. Follow up imaging will continue every 2-3 months for up to 4 years. Percent deposition of Lipiodol in the targeted tumor was assessed using 3D quantitative analysis on the 24hr post-TACE CT. Tumor response using RECIST, EASL, modified RECIST, tumor volume (volumetric RECIST), and volumetric tumor enhancement (quantitative EASL) were performed on the DCE-MRI, CT, and PET-CT, and correlated with Lipiodol deposition. Spearman rank correlation coefficient and Pearson’s product-moment correlation were used. The Kaplan-Meier method with the log-rank test was used to assess whether Lipiodol is a biomarker of survival. 12/30 patients with HCC and 12/30 patients with hepatic metastases have been enrolled (#NCT01877187). Clinical trial information: NCT01877187.

SIR-Spheres ® radioembolization in the management of metastatic colorectal cancer: a medical oncology perspective

SUMMARY Despite of the recent advances in personalized medicine, the majority of patients with metastatic colorectal cancer still succumb to disease progression, with liver failure constituting one of the most common causes of death. Recently, selective internal radioembolization has emerged as a new treatment option in patients with liver predominant disease. The concurrent administration of yttrium-90 (Y-90) SIR-Spheres® (SIRTEX, Sydney, Australia) microspheres and chemotherapy has been linked to significant improvements in response rate, time to intrahepatic tumor progression and overall survival. In this manuscript, the author provides his personal perspective on the current clinical evidence in support of SIR-Spheres liver embolization and reflects on the potential of this treatment in various stages of treatment of metastatic colorectal cancer.

Therapeutic strategies for neuroendocrine liver metastases.

Patients who have neuroendocrine tumors frequently present with liver metastases. A wide panel of treatment options exists for these patients. Liver resection with curative intent achieves the best long-term results. Highly selected patients may be considered for liver transplantation. Substantial recurrence rates reported after surgical approaches call for neoadjuvant and adjuvant concepts. Liver-directed, locally ablative procedures are recommended for patients with limited, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, transarterial chemoembolization, and selective internal radiotherapy, offer excellent palliation for patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising palliative procedure for patients with hepatic and/or extrahepatic metastases. The efficacy of these treatment options needs to be evaluated in randomized trials. Somatostatin analogues have demonstrated effectiveness not only for symptomatic relief in patients with secreting tumors but also for the control of proliferation in small intestinal neuroendocrine tumors and most recently also in those originating from the pancreas. Chemotherapy is an option mainly for those with pancreatic neuroendocrine tumors and high-grade tumors irrespective of the origin. Novel drugs targeting specific pathways within the tumor cell have produced improved progression-free survival compared with placebo in patients with pancreatic neuroendocrine tumors. Despite such a diverse armamentarium, there is uncertainty with regard to the optimal treatment regimens. Newly introduced molecular-based markers, along with the conduction of clinical trials comparing the efficacy of treatment modalities, offer a chance to move the treatment of neuroendocrine tumor disease toward personalized patient care. In this report, the authors review the approaches for treatment of neuroendocrine liver metastases, identify shortcomings, and anticipate future perspectives. Furthermore, clinical practice recommendations are provided for currently available treatment options. Although multiple modalities are available for the treatment of neuroendocrine liver metastases, optimal management is unclear. The current knowledge pertaining to these treatment options is analyzed.

Y-90 microsphere selective internal radiation treatment (SIRT) in treatment of primary and metastatic liver cancer.

e15174 Background: Y-90 SIRT is rapidly emerging as an effective treatment modality in patients with liver predominant disease. Aims: #1 Assess comparative efficacy and toxicity between Y-90 resin ...

Response rates to hepatic arterial infusion (HAI) pump therapy in patients with metastatic colorectal cancer liver metastases (mCRC LM) after progression on all standard chemotherapies.

597 Background: To evaluate the overall response rate of HAI with floxuridine (FUDR) in the refractory setting in patients with mCRC LM. Methods: After obtaining an IRB waiver a computerized search was performed for patients with mCRC treated with 5FU, oxaliplatin and irinotecan +/- EGFR and VEGF inhibitor from 2003-2012. Charts were reviewed to ensure patients (pts) had received all standard therapies prior to HAI pump placement. All pts received HAI FUDR and no new systemic targeted or cytotoxic therapies were used with HAI pump. Imaging was re-reviewed for confirmation of progression prior to HAI pump placement and for best response using RECIST 1.1 criteria. Results: 75 pts were identified; of these 23 had radiographic disease progression on all standard chemotherapies (5FU, irinotecan and oxaliplatin) prior to having a pump placed. Of the 23 evaluable pts, the median age was 53 (range 37-75). Six pts had low volume extrahepatic metastases at the time of pump placement. The overall response rate (ORR) was 8/23 (35%); 10/23 (43%) pts had stable disease (SD). The median duration of SD was 4 months (range 1-10). Median follow up, measured from the date of HAI initiation, was 24 months and median overall survival (OS) was 22 months (95% CI 13-16). The median hepatic progression free survival (hPFS) was 4.5 months [CI: 3.8-6.7]. Thirteen pts developed extrahepatic disease progression (including 5 pts with preexisting extrahepatic disease). The median overall PFS was 3.9 months [95% CI 2.24-5.33]. Median number of HAI treatments was 4 cycles (range 1-13). Six out of 23 (26%) pts required a 50-75% dose reduction by the second cycle due to elevated liver function tests and 18/23 (78%) required a dose reduction after the 3rd cycle. No pts required stents or developed long term liver or biliary toxicity. Conclusions: In a cohort of 23 patients with mCRC LM, refractory to all standard agents, treatment with HAI FUDR resulted in an ORR by RECIST 1.1 of 35% and median OS of 22 months. Further studies focusing on locoregional therapy in patients with liver predominant disease are warranted. Studies to molecularly characterize these tumors are ongoing.

Hepatic Arterial Therapy with Drug-Eluting Beads in the Management of Metastatic Pancreatic Carcinoma to the Liver: A Multi-Institutional Registry

Introduction. There has been limited reporting on the use of hepatic-directed therapy in liver dominant hepatic metastases arising from pancreatic cancer. Methods. An IRB-approved prospective multi-institutional treatment registry of 885 patients undergoing 1458 treatments for primary or secondary cancers in the liver was evaluated from January 2007 to January 2011. Results. Ten patients underwent a total of 17 treatment sessions with drug-eluting beads (DEBs). Six patients received concurrent chemotherapy while undergoing DEB with no severe adverse events. After a median followup of 16 months, the 6- and 12-month response rates were 80% and 75%, respectively, with a median overall survival of 9.3 months. Conclusion. Hepatic arterial therapy with DEB can be safely and effectively used in selected patients with liver predominant metastatic disease from pancreatic cancer. This therapy should be considered in combination with systemic chemotherapy as a possible second therapy given the limited response rates of second-line chemotherapy.

Hepatic Arterial Therapy with Drug-Eluting Beads in the Management of Metastatic Bronchogenic Carcinoma to the Liver: A Multi-Institutional Registry

Introduction. There has been limited information reported on the use of hepatic arterial therapy in liver dominant hepatic metastases arising from lung cancer. The aim of this study was to evaluate the safety and efficacy of hepatic arterial therapy in the treatment of liver dominant hepatic metastases arising from lung cancer. Methods. Thirteen patients underwent a total of 30 treatment sessions with Drug-Eluting Beads. Eight of the thirteen received only doxorubicin DEB (17 of the total treatments), and four patients received Irinotecan DEB (7 of the total treatments). Results. The planned preprocedural dosage was a median of 75 mg (range 19–200), with total hepatic dose exposure being a median of 150 mg (range 0–458), with a technical success rate of 97% in all 29 treatments. There were 4 adverse events related to treatment, but no evidence of hepatic insufficiency. Overall 6-month and 12-month response rates were 50%. After a median followup of 24 months, the median overall survival in this cohort was 14 months (range 7–48 months). Conclusion. Drug-eluting beads loaded with doxorubicin (DEBDOX) or irinotecan (DEBIRI) can be safely and effectively used in treatment of patients with liver predominant metastatic disease from lung cancer.